Transcriptome Analysis Identifies An ASD-Like Phenotype In Oligodendrocytes And Microglia From C58/J Amygdala That Is...

Area of Science:

• Neuroscience
• Genetics
• Developmental Biology

Background:

• Autism Spectrum Disorder (ASD) is a neurodevelopmental condition affecting communication and social behavior, with higher prevalence in males.
• Investigating the brain mechanisms underlying sociability deficits and sex differences in ASD is crucial for understanding the disorder.
• This study utilizes a mouse model to explore the neurobiological underpinnings of ASD-related social behaviors.

Approach:

• Sociability was assessed in C58/J and C57BL/6J mice using the 3-chamber social choice test.
• Transcriptional and epigenetic changes in the amygdala were analyzed using bulk and single-nucleus RNA sequencing (snRNA-Seq) and DMRseq.
• Gene regulatory networks and cell communication pathways were examined to understand cellular mechanisms.

Key Points:

• C58/J mice exhibited varied social behaviors, with distinct immune-related transcriptional signatures in the amygdala compared to C57BL/6J mice.
• snRNA-Seq identified altered oligodendrocyte and microglia gene expression in C58/J mice, suggesting impaired myelination linked to ASD risk genes, sex, and sociability.
• Analysis revealed diminished oligodendrocyte/microglia differentiation and altered gene regulatory networks, with oxytocin showing potential benefits for myelin gene expression.

Conclusions:

• The C58/J mouse model effectively captures sex and sociability influences on brain transcriptomes relevant to ASD.
• Single-nucleus transcriptome analysis highlights the potential roles of oligodendrocytes and microglia in ASD pathophysiology.
• Findings offer insights into disrupted gene regulation, cell differentiation, and epigenetic processes contributing to social behavior deficits in ASD.